Campylobacter is among the most common causes of bacterial diarrhea in children worldwide. Infection by pathogenic Campylobacter is inhibited in vitro and in vivo by human milk oligosaccharides. The oligosaccharides responsible for this inhibition contain fucose linked by an alpha 1, 2 glycosidic bond. These linkages are produced by the 2-fucosyltransferase of milk that is the product of the secretor gene, FUT2. The purpose of this study is to determine whether these oligosaccharides also protect against related enteric pathogens, such as V. cholerae; to determine whether natural variation in maternal fucosyltransferases (differences in FUT2) is associated with differences in the risk of diarrhea in breast-fed infants; and to find the simplest alpha1, 2 linked fucosylooligosaccharides that protect infants from campylobacter and related causes of diarrhea. To achieve these goals, we propose the following specific aims: 1. Characterize the Campylobacter adhesin associated with binding to host cell receptors. 2. Define the molecular basis for affinity of Campylobacter and V. cholerae to alpha 1, 2-linked histo-blood group antigen of epithelial cells, and for inhibition of such binding by human milk oligosaccharides. 3. Determine the genetic polymorphisms that underlie maternal and infant secretor and Lewis phenotypes and relate these to heterogeneity in human milk oligosaccharide expression and risk of bacterial diarrheal in breastfed infants. 4. Measure the safety, tolerance and efficacy of the human milk oligosaccharide 2'-fucosyllactose, and related compounds, to protect against Campylobacter and related pathogens in mice. The increased understanding of the pathophysiology of Campylobacter and related pathogens that would result from these studies would allow identification of infants and high risk for these pathogens, and would provide and novel prophylactic and/or therapeutic agents that would be used to prevent and/or treat infections with Campylobacter and related pathogens.